Potential liver damage due to co-exposure to As, Cd, and Pb in mining areas: Association analysis and research trends from a Chinese perspective

There is global concern regarding the public health hazards of environmental exposure to multiple toxic heavy metals. The effects of toxic heavy metals on liver function have been suggested in previous reports, but the association between exposure to multiple toxic heavy metals and liver function has not been elucidated. The aim of this study was to investigate the effects of exposure to multiple toxic heavy metals, arsenic(As), lead(Pb), and cadmium(Cd), on liver function through population-based and animal studies. A total of 3590 participants were enrolled from the mining areas in Western Hunan Province. The concentrations of As, Pb, and Cd in the urine and plasma samples were determined using quadrupole inductively coupled plasma mass spectrometry (ICP-MS). Bayesian kernel machine regression (BKMR) was employed for the joint association assay. An animal study was conducted to further verify the cumulative effects of metals on liver damage-related parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels. Research trends regarding toxic metals were also explored to obtain in-depth understanding of the current knowledge in this field. Typically, for single-exposure analysis, in most mines, Pb exhibited a significantly negative association with ALT levels, whereas for cumulative effects analysis, when As, Pb, and Cd concentrations were at the 50thpercentile, a significantly negative effect on liver ALT levels was observed. Furthermore, animal studies have shown that co-exposure to As, Pb, and Cd could aggravate liver dysfunction in mice compared to that in the single-metal treated group (p